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Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Request for Comments

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Information about this document as published in the Federal Register.

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AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice; request for comments.

SUMMARY:

The Food and Drug Administration (FDA) is requesting comments, including scientific and other information, concerning the harmful and potentially harmful constituents (HPHCs) in tobacco products and tobacco smoke. This information will assist the Agency in establishing a list of HPHCs in tobacco products and tobacco smoke (the HPHC list).

DATES:

Submit either electronic or written comments by October 11, 2011.

ADDRESSES:

Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Identify comments with the docket number found in brackets in the heading of this document.

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FOR FURTHER INFORMATION CONTACT:

Carol Drew, Center for Tobacco Products, Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 20850-3229, 877-287-1373.

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SUPPLEMENTARY INFORMATION:

I. Background

On June 22, 2009, the President signed the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) (Pub. L. 111-31) into law. The Tobacco Control Act amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 301 et seq.) by, among other things, adding a new chapter granting FDA important new authority to regulate the manufacture, marketing, and distribution of tobacco products to protect the public health generally and to reduce tobacco use by minors. Section 904(e) of the FD&C Act (21 U.S.C. 387d(e)), as added by the Tobacco Control Act, requires FDA to establish, and periodically revise as appropriate, “a list of harmful and potentially harmful constituents, including smoke constituents, to health in each tobacco product by brand and by quantity in each brand and subbrand.” Section 904(e) of the FD&C Act also requires that FDA “publish a public notice requesting the submission by interested persons of scientific and other information concerning the harmful and potentially harmful constituents in tobacco products and tobacco smoke.”

The Agency has solicited scientific and other information from interested persons and has developed a list of tobacco product constituents it currently believes are harmful or potentially harmful to health. Although the Agency's work to date reflects consideration of substantial scientific and other information, we believe that additional information from the public may be beneficial to the Agency before it establishes the list described in section 904(e) of the FD&C Act. We are therefore publishing the Agency's Start Printed Page 50227current list as table 1 of this document and requesting public comment as described in section II of this document. In this section of the document, we are also providing information about the Agency's guidance on HPHCs, the criteria that the Agency used to help develop the list, and reasons the Agency might add or remove constituents.

On June 10, 2010, FDA announced the availability for public comment of a draft guidance for industry and FDA staff entitled “Harmful and Potentially Harmful Constituents' in Tobacco Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act” (75 FR 32952). FDA announced the availability of the final guidance on January 31, 2011 (76 FR 5387) (available at http://www.fda.gov/​TobaccoProducts/​GuidanceComplianceRegulatoryInformation) (HPHC final guidance). This final guidance represents the Agency's current thinking on the meaning of the term “harmful and potentially harmful constituent” in the context of implementing section 904(e) of the FD&C Act. It states: “FDA believes that the phrase 'harmful and potentially harmful constituent' includes any chemical or chemical compound in a tobacco product or in tobacco smoke: (a) That is or potentially is inhaled, ingested, or absorbed into the body; and (b) that causes or has the potential to cause direct or indirect harm to users or non-users of tobacco products.”(HPHC final guidance at page 2). The HPHC final guidance includes examples of constituents that have the potential to cause direct harm and examples of constituents that have the potential to cause indirect harm: “Examples of constituents that have the 'potential to cause direct harm' to users or non-users of tobacco products include constituents that are toxicants, carcinogens, and addictive chemicals and chemical compounds. Examples of constituents that have the 'potential to cause indirect harm' to users or non-users of tobacco products include constituents that may increase the exposure to the harmful effects of a tobacco product constituent by: (1) Potentially facilitating initiation of the use of tobacco products; (2) potentially impeding cessation of the use of tobacco products; or (3) potentially increasing the intensity of tobacco product use (e.g., frequency of use, amount consumed, depth of inhalation). Another example of a constituent that has the 'potential to cause indirect harm' is a constituent that may enhance the harmful effects of a tobacco product constituent.” (HPHC final guidance at page 2).

On May 1, 2010, the Agency established a subcommittee of the Tobacco Products Scientific Advisory Committee (TPSAC), [1] the Tobacco Product Constituents Subcommittee (the subcommittee), and charged the subcommittee with making preliminary recommendations to TPSAC on HPHCs in tobacco products and tobacco smoke. The subcommittee held public meetings on June 8 and 9, 2010, and July 7, 2010. Prior to these meetings, FDA solicited data, information, and/or views on HPHCs in tobacco products and tobacco smoke from the public, and at the June meeting, presentations were made by interested persons.[2] At these meetings the subcommittee:

  • Reviewed example lists of HPHCs developed by other countries and organizations;
  • Identified criteria for selecting carcinogens, toxicants, and addictive chemicals or chemical compounds in tobacco products and tobacco smoke;
  • Identified chemicals or chemical compounds that met the identified criteria;
  • Confirmed the existence of methods for measuring each chemical or chemical compound identified; and
  • Identified other potentially important information or criteria for measuring HPHCs in tobacco products or tobacco smoke, such as smoking machine regimens to be used in measuring HPHCs.

The subcommittee made preliminary recommendations to TPSAC.

On August 30, 2010, TPSAC held a public meeting to deliberate on the recommendations from the subcommittee. Prior to this meeting, FDA published a notice in the Federal Register soliciting data, information, and/or views from the public on the issues to be discussed at this meeting.[3] FDA asked what criteria TPSAC recommended the Agency use for determining whether a constituent is a carcinogen, toxicant, or addictive chemical or chemical compound that should be included on the HPHC list. As a result of its discussions, TPSAC recommended to the Agency the following criteria for selecting the HPHC list:

  • Constituents identified as known, likely, probably, or possible human carcinogens by the U.S. Environmental Protection Agency (EPA);
  • Constituents identified as known, probable, or possible carcinogens by the International Agency for Research on Cancer (IARC) including IARC Group 1 (carcinogenic to humans), IARC Group 2 (probably carcinogenic to humans), and IARC Group 2B (possibly carcinogenic to humans);
  • Constituents identified as human carcinogens or reasonably anticipated to be human carcinogens by the National Toxicology Program (NTP);
  • Constituents identified as potential occupational carcinogens by the National Institute for Occupational Safety and Health (NIOSH):
  • Constituents identified by EPA or the Agency for Toxic Substances and Disease Registry (ATSDR) as having adverse respiratory or cardiac effects;
  • Constituents identified by the California Environmental Protection Agency (CA EPA) as reproductive or developmental toxicants;
  • Constituents having, based upon a review of the peer-reviewed literature, evidence of at least two of the following measures of abuse liability (addiction):

○ Central nervous system activity;

○ Animal drug discrimination;

○ Conditioned place preference;

○ Animal self-administration;

○ Human self-administration;

○ Drug liking;

○ Signs of withdrawal; and

  • Constituents banned in food (for smokeless tobacco products).

FDA believes having criteria for use in determining whether a constituent is harmful or potentially harmful will be beneficial. FDA carefully evaluated the data, information, and views on HPHCs in tobacco products provided by TPSAC and the public, in light of the Agency's own knowledge and expertise, and taking into consideration its HPHC final guidance. Based on this evaluation, FDA tentatively concludes that it should use the criteria listed previously in this document in determining whether a constituent should be included on the HPHC list. Specifically, FDA has tentatively concluded that it should consider a constituent meeting these criteria to be harmful or potentially harmful, such that it should be included on the HPHC list, unless other scientific information obtained by or submitted to the Agency shows that the constituent is Start Printed Page 50228not, in fact, harmful or potentially harmful. Applying this approach to the criteria and the available information, FDA developed table 1 of this document.

FDA recognizes that table 1 of this document may not include all constituents that are “harmful or potentially harmful.” For example, the criteria described previously in this document generally depend on a chemical or chemical compound being both studied and listed by another entity, such as constituents identified by EPA or ATSDR as having adverse respiratory or cardiac effects. The fact that a constituent has not been so identified by EPA or ATSDR could be because it has not been adequately studied or has not yet been systematically reviewed by relevant agencies, rather than because the constituent does not have adverse respiratory or cardiac effects. Moreover, FDA has only focused on the five disease outcomes of cancer, cardiovascular disease, respiratory effects, developmental or reproductive effects, and addiction. FDA intends to review other disease outcomes to assess whether additional chemicals or chemical compounds in tobacco products or tobacco smoke are harmful or potentially harmful constituents that contribute to the risk of other diseases. Similarly, the criteria FDA has tentatively selected are limited to those that relate to carcinogens, toxicants, and addictive chemicals or chemical compounds in tobacco products and tobacco smoke. We intend to consider whether additional criteria should be selected to help identify other classes of harmful or potentially harmful chemicals and chemical compounds for inclusion on the HPHC list, and whether individual constituents should be added. Just as these types of new information may lead to additions to the list, FDA recognizes that it may become aware of new scientific information about constituents of tobacco products that make it appropriate to remove one or more of the constituents that appear on the list. For these reasons, FDA will continue to review scientific information about tobacco product constituents. FDA intends to do this both before and after it establishes its list of HPHCs for the purpose of section 904(e) of the FD&C Act, consistent with the directive in section 904(e) that the Agency periodically revise the list as appropriate.

II. Request for Comments and Information

FDA is soliciting public comment, including scientific and other information, concerning the HPHCs in tobacco products and tobacco smoke. We are particularly interested in comments from the public on the following topics:

  • The criteria FDA should use in determining whether a constituent is harmful or potentially harmful such that it should be included on the HPHC list;
  • Whether any chemicals or chemical compounds not listed in table 1 of this document should be added because they are harmful or potentially harmful, including supporting scientific or other information; and/or
  • Whether any of the chemicals or chemical compounds listed in table 1 of this document should be removed because they are not harmful or potentially harmful, including supporting scientific or other information.

III. Submission of Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) either electronic or written comments regarding this document. It is only necessary to send one set of comments. It is no longer necessary to send two copies of mailed comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

Table 1—List of the Chemicals and Chemical Compounds Identified by FDA as Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke

ConstituentCarcinogen (CA), respiratory toxicant (RT), cardiovascular toxicant (CT), reproductive or developmental toxicant (RDT), addictive (AD)
AcetaldehydeCA, RT, AD
AcetamideCA
AcetoneRT
AcroleinRT, CT
AcrylamideCA
AcrylonitrileCA, RT
Aflatoxin B1CA
4-AminobiphenylCA
1-AminonaphthaleneCA
2-AminonaphthaleneCA
AmmoniaRT
AnabasineAD
o-AnisidineCA
ArsenicCA, CT, RDT
A-α-C (2-Amino-9 H-pyrido[2,3-b]indole)CA
Benz[a]anthraceneCA, CT
Benz[j]aceanthryleneCA
BenzeneCA, CT, RDT
Benzo[b]fluorantheneCA, CT
Benzo[k]fluorantheneCA, CT
Benzo[b]furanCA
Benzo[a]pyreneCA
Benzo[c]phenanthreneCA
BerylliumCA
1,3-ButadieneCA, RT, RDT
CadmiumCA, RT, RDT
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Caffeic acidCA
Carbon monoxideRDT
CatecholCA
Chlorinated dioxins/furansCA, RDT
ChromiumCA, RT, RDT
ChryseneCA, CT
CobaltCA, CT
CoumarinBanned in food
Cresols (o-, m-, and p-cresol)CA, RT
CrotonaldehydeCA
Cyclopenta[c,d]pyreneCA
Dibenz[a,h]acridineCA, CT
Dibenz[a,j]acridineCA
Dibenz[a,h]anthraceneCA
Dibenzo[c,g]carbazoleCA
Dibenzo[a,e]pyreneCA
Dibenzo[a,h]pyreneCA
Dibenzo[a,i]pyreneCA
Dibenzo[a,l]pyreneCA
2,6-DimethylanilineCA
Ethyl carbamate (urethane)CA, RDT
EthylbenzeneCA
Ethylene oxideCA, RT, RDT
FormaldehydeCA, RT
FuranCA
Glu-P-1 (2-Amino-6-methyldipyrido[1,2-a: 3',2'-d]imidazole)CA
Glu-P-2 (2-Aminodipyrido[1,2-a: 3',2'-d]imidazole)CA
HydrazineCA, RT
Hydrogen cyanideRT, CT
Indeno[1,2,3-cd]pyreneCA
IQ (2-Amino-3-methylimidazo[4,5-f]quinoline)CA
IsopreneCA
LeadCA, CT, RDT
MeA-α-C (2-Amino-3-methyl)-9 H-pyrido[2,3-b]indole)CA
MercuryCA, RDT
Methyl ethyl ketoneRT
5-MethylchryseneCA
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)CA
NaphthaleneCA, RT
NickelCA, RT
NicotineRDT, AD
NitrobenzeneCA, RT, RDT
NitromethaneCA
2-NitropropaneCA
N-Nitrosodiethanolamine (NDELA)CA
N-NitrosodiethylamineCA
N-Nitrosodimethylamine (NDMA)CA
N-NitrosomethylethylamineCA
N-Nitrosomorpholine (NMOR)CA
N-Nitrosonornicotine (NNN)CA
N-Nitrosopiperidine (NPIP)CA
N-Nitrosopyrrolidine (NPYR)CA
N-Nitrososarcosine (NSAR)CA
NornicotineAD
PhenolRT, CT
PhIP (2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine)CA
Polonium-210CA
PropionaldehydeRT, CT
Propylene oxideCA, RT
QuinolineCA
SeleniumRT
StyreneCA
o-ToluidineCA
TolueneRT, RDT
Trp-P-1 (3-Amino-1,4-dimethyl-5 H-pyrido[4,3-b]indole)CA
Trp-P-2 (1-Methyl-3-amino-5 H-pyrido[4,3-b]indole )CA
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Uranium-235CA, RT
Uranium-238CA, RT
Vinyl acetateCA, RT
Vinyl chlorideCA
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Dated: August 9, 2011.

Leslie Kux,

Acting Assistant Commissioner for Policy.

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Footnotes

[FR Doc. 2011-20502 Filed 8-11-11; 8:45 am]

BILLING CODE 4160-01-P